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              Advocacy & Research for Unlimited Lifespans


MDI Biological Scientists Identify Pathways That Extend Lifespan by 500 Percent in Nematodes

aging mrna translation uprmt ampk germline daf-2 rsks-1 c. elegans

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#1 Engadin

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Posted 09 January 2020 - 10:19 AM







A R T I C L E ' S   S O U R C E :   MDI Biological Laboratory


F U L L   T E X T   P R I M A L   T E X T :   Cell Reports (Translational Regulation of Non-autonomous Mitochondrial Stress Response Promotes Longevity)






Discovery of Cellular Mechanisms Could Open Door to More Effective Anti-Aging Therapies



Scientists at the MDI Biological Laboratory, in collaboration with scientists from the Buck Institute for Research on Aging in Novato, Calif., and Nanjing University in China, have identified synergistic cellular pathways for longevity that amplify lifespan fivefold in C. elegans, a nematode worm used as a model in aging research.

The increase in lifespan would be the equivalent of a human living for 400 or 500 years, according to one of the scientists.
The research draws on the discovery of two major pathways governing aging in C. elegans, which is a popular model in aging research because it shares many of its genes with humans and because its short lifespan of only three to four weeks allows scientists to quickly assess the effects of genetic and environmental interventions to extend healthy lifespan.
Because these pathways are “conserved,” meaning that they have been passed down to humans through evolution, they have been the subject of intensive research. A number of drugs that extend healthy lifespan by altering these pathways are now under development. The discovery of the synergistic effect opens the door to even more effective anti-aging therapies.
The new research uses a double mutant in which the insulin signaling (IIS) and TOR pathways have been genetically altered. Because alteration of the IIS pathways yields a 100 percent increase in lifespan and alteration of the TOR pathway yields a 30 percent increase, the double mutant would be expected to live 130 percent longer. But instead, its lifespan was amplified by 500 percent.
“Despite the discovery in C. elegans of cellular pathways that govern aging, it hasn’t been clear how these pathways interact,” said Hermann Haller, M.D., president of the MDI Biological Laboratory. “By helping to characterize these interactions, our scientists are paving the way for much-needed therapies to increase healthy lifespan for a rapidly aging population.”
The elucidation of the cellular mechanisms controlling the synergistic response is the subject of a recent paper in the online journal Cell Reports entitled “Translational Regulation of Non-autonomous Mitochondrial Stress Response Promotes Longevity.” The authors include Jarod A. Rollins, Ph.D., and Aric N. Rogers, Ph.D., of the MDI Biological Laboratory.
“The synergistic extension is really wild,” said Rollins, who is the lead author with Jianfeng Lan, Ph.D., of Nanjing University. “The effect isn’t one plus one equals two, it’s one plus one equals five. Our findings demonstrate that nothing in nature exists in a vacuum; in order to develop the most effective anti-aging treatments we have to look at longevity networks rather than individual pathways.”
The discovery of the synergistic interaction could lead to the use of combination therapies, each affecting a different pathway, to extend healthy human lifespan in the same way that combination therapies are used to treat cancer and HIV, Pankaj Kapahi, Ph.D., of the Buck Institute, has said. Kapahi is a corresponding author of the paper with Rogers and Di Chen, Ph.D., of Nanjing University.
The synergistic interaction may also may explain why scientists have been unable to identify a single gene responsible for the ability of some people to live to extraordinary old ages free of major age-related diseases until shortly before their deaths.
The paper focuses on how longevity is regulated in the mitochondria, which are the organelles in the cell responsible for energy homeostasis. Over the last decade, accumulating evidence has suggested a causative link between mitochondrial dysregulation and aging. Rollins’ future research will focus on the further elucidation of the role of mitochondria in aging, he said.
The research was conducted at the MDI Biological Laboratory and Nanjing University using information from double mutants developed by Kapahi. Rollins’ and Rogers’ work was supported by the National Institutes of Health (AG056743), the Morris Scientific Discovery Fund and the National Institute of General Medical Sciences (P20GM103423 and P20GM104318).

#2 eighthman

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Posted 12 January 2020 - 12:31 AM

Next question, what supplements are likely to duplicate these changes in gene expression?  Sounds like Rapamycin, resveratrol............maybe emodium?

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#3 Decimus

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Posted 12 January 2020 - 08:08 AM

Next question, what supplements are likely to duplicate these changes in gene expression?  Sounds like Rapamycin, resveratrol............maybe emodium?

Obviously, nothing is going to come close to duplicating these changes in humans, as our metabolism is thousands of times more complex than a c elegan, but yes you would be downregulating mTOR and IGF-1.  Rapa would cover the mTOR.  Any number of things will downregulate IGF-1, metformin, glucosamine etc., but these supplements have been tried in mouse study before and the results were nowhere near as impressive.  


I’m not sure why the results were so impressive in nematodes this time around.  I suspect it was because it was an immediate genetic alteration which has a more pronounced and permanent affect than a supplement and/or they found a slightly different pathway to mimic CR via DAF-2.  But I don’t see anything in this study that gives us new insight into which supplements to take or not to take, unfortunately. 

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#4 eighthman

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Posted 12 January 2020 - 01:16 PM



Rapamycin and curcumin, perhaps. The study looks big for nematodes and probably marginal for us.

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#5 Kentavr

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Posted 15 January 2020 - 04:14 PM

I think the advantage of NMN is provided by that phosphate group. When you take NMN, the cell does not need to look for phosphate, which means that the cell cannot reduce the production of NAD + by limiting the availability of the phosphate group (even assuming that NMN breaks down into NR and a phosphate group to enter the cell).
It makes no difference to me what happens in the process if the result is better than from NR.

Elk (scientist): "It's impossible! It is impossible for carrots to fall from the sky in the form of rain!"

Rabbit: ”You don’t understand: I’m not interested in WHY this can’t happen if I get the desired result."

I want to hear an explanation why NMN allows you to create more NAD + molecules than NR, and why there are no negative effects from it.

Edited by Kentavr, 15 January 2020 - 04:23 PM.

Also tagged with one or more of these keywords: aging, mrna translation, uprmt, ampk, germline, daf-2 rsks-1, c. elegans

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